Semaphorin 4A antibody alleviates arsenic-induced hepatotoxicity in mice via inhibition of AKT2/NF-κB inflammatory signaling

Yang, Yuan; Wang, Qinling; Wang, Wenjuan; Wei, Shaofeng; Zeng, Qibing; Zhang, Aihua

doi:10.1016/j.taap.2020.115364

Cited by 7 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other studies have demonstrated that kaempferol exerts its anti-inflammatory effects in cardiac fibroblasts [ 30 ] and reduces inflammation in an LPS-induced acute lung-injury model [ 31 ] by inhibiting Akt phosphorylation. It is worth noting that Akt activation has also been linked to NF-κB activation in other studies [ 32 , 33 ]. In our study, we found that CCl 4 treatment increased the levels of PI3K and phosphorylated Akt in the liver, while kaempferol treatment reduced Akt phosphorylation.…”

Section: Discussionmentioning

confidence: 86%

Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways

Lee

Yoon

Moon

2023

IJMS

View full text Add to dashboard Cite

Oxidative stress plays a critical role in the development of liver disease, making antioxidants a promising therapeutic approach for the prevention and management of liver injuries. The aim of this study was to investigate the hepatoprotective effects of kaempferol, an antioxidant flavonoid found in various edible vegetables, and its underlying mechanism in male Sprague-Dawley rats with carbon tetrachloride (CCl4)-induced acute liver damage. Oral administration of kaempferol at doses of 5 and 10 mg/kg body weight resulted in the amelioration of CCl4-induced abnormalities in hepatic histology and serum parameters. Additionally, kaempferol decreased the levels of pro-inflammatory mediators, TNF-α and IL-1β, as well as COX-2 and iNOS. Furthermore, kaempferol suppressed nuclear factor-kappa B (NF-κB) p65 activation, as well as the phosphorylation of Akt and mitogen-activated protein kinase members (MAPKs), including extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 in CCl4-intoxicated rats. In addition, kaempferol improved the imbalanced oxidative status, as evidenced by the reduction in reactive oxygen species levels and lipid peroxidation, along with increased glutathione content in the CCl4-treated rat liver. Administering kaempferol also enhanced the activation of nuclear factor-E2-related factor (Nrf2) and heme oxygenase-1 protein, as well as the phosphorylation of AMP-activated protein kinase (AMPK). Overall, these findings suggest that kaempferol exhibits antioxidative, anti-inflammatory, and hepatoprotective effects through inhibiting the MAPK/NF-κB signaling pathway and activating the AMPK/Nrf2 signaling pathway in CCl4-intoxicated rats.

show abstract

Section: Discussionmentioning

confidence: 86%

Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways

Lee

Yoon

Moon

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…According to earlier research, NRP1 is likely to play a dual role in the process of osteoblasts differentiating into osteocytes, directly promoting differentiation while maintains the fine balance in osteogenesis [ 39 ]. Furthermore, in a mouse model of hepatotoxicity, upregulation of SEMA3A and its receptor NRP-1 synergistically inhibited the Akt2 /NF-κB and NLRP3 inflammatory signaling pathways [ 40 ]. This positive correlation between SEMA3A and NRP-1 was also observed in the present study, in addition to the diminished effect of SEMA3A overexpression by NRP-1 depletion on LPS-induced chondrocyte inflammation and apoptosis as well as cartilage matrix degradation.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Zhang

Lü

et al. 2021

Bioengineered

View full text Add to dashboard Cite

Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.

show abstract

“…Regarding the arsenic-induced hepatic toxicity, the underlying mechanism demonstrated as the imbalance of oxidant-antioxidant, the elevations of pro-inflammatory cytokines, DNA damage, apoptotic cell death, and pyroptosis [ 3 , 4 ]. Moreover, our study show arsenic induced the increased levels of proinflammatory cytokines IL-1β, IL-6, and NLRP3 inflammasome in mouse liver [ 5 ]. The liver is a frontline immune tissue, and liver function is associated closely with immune response, excessive inflammation in the absence of infection leads to sterile liver injury and tissue damage [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Lentinan alleviates arsenic-induced hepatotoxicity in mice via downregulation of OX40/IL-17A and activation of Nrf2 signaling

Yang

Song

Yuan-yuan

et al. 2022

BMC Pharmacol Toxicol

Self Cite

View full text Add to dashboard Cite

Background Arsenic, existing ubiquitously in soil, drinking water, or food, is well known to be an environmental pollutants concerned by European Food Safety Authority. Lentinan, a beta-1,6;1,3-glucan extracts from Lentinus edodes, which has the properties of antioxidant and immunomodulation, present study explored the pharmacological effects of Lentinan on arsenic induced hepatotoxicity in mice. Methods Mice experiments were performed by sodium arsenite (SA) treatment or Lentinan intervention, then histopathology, ELISA, Flow Cytometry, or Western-Blotting were applied to evaluate hepatic injury, oxidative stress, CD4+ type 17 helper T (Th17) cells, CD4+CD25+Foxp3+ regulatory T cells (Tregs), T cells receptor OX40/CD134, IL-17A, NLRP3, Nrf2, and NQO1. Results SA treatment showed hepatic pathological injury and the elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in serum, and induced the increases of malondialdehyde (MDA), Th17 cells, OX40 or IL-17A in liver tissues, which were consistently ameliorated by Lentinan intervention. Further, immunoblotting experiments showed that Lentinan intervention downregulated the levels of OX40, IL-17A, and NLRP3 signals, while elevated the levels of anti-oxidative Nrf2, NQO1 signals compared to arsenic treatment group. For Tregs, Lentinan intervention showed no significant difference from SA treatment group. Conclusion Lentinan antagonizes SA-induced hepatotoxicity in mice, may be involved in the downregulations of pro-inflammatory OX40 or IL-17A and the activation of anti-oxidative Nrf2, NQO1 signals.

show abstract

Semaphorin 4A antibody alleviates arsenic-induced hepatotoxicity in mice via inhibition of AKT2/NF-κB inflammatory signaling

Cited by 7 publications

References 27 publications

Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways

Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways

Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Lentinan alleviates arsenic-induced hepatotoxicity in mice via downregulation of OX40/IL-17A and activation of Nrf2 signaling

Contact Info

Product

Resources

About